Professor & patients' paper on the solvable biological challenge of ME/CFS: reader-friendly version
Simon McGrath provides a patient-friendly version of a peer-reviewed paper which highlights some of the most promising biomedical research on ME/CFS ...
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Pyruvate dehydrogenase deficiency does not lead to fatigue: Fluge & Mella's PDH impairment revisited

Discussion in 'Latest ME/CFS Research' started by Hip, Nov 28, 2017.

  1. rodgergrummidge

    rodgergrummidge

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    I know that many hold strong beliefs on the 'toxins in CFS' theory. I dont want to totally dismiss the theory. But I think it might be useful to discuss why such a theory has such wide intuitive appeal despite significant contrary clinical evidence.

    The possibility that toxins in our environment/foods may somehow build up in our bodies and poison our mitochondria leading to decreased ATP production and fatigue certainly sounds like a plausible and attractive model for CFS. A quick google search shows that the internet is full of Business Models that work on basis that i) You have been poisoned by your Westernized life-style and ii) You can be treated (and cured) using Our Detox program/products/supplements/etc/etc. The arsenic example suggested above is clearly is a mitochondrial poison that is highly toxic. But the current restricted use of arsenic together with its known historical use combined with the known epidemiology of CFS make it highly unlikely be a causal (or even a contributing) factor to mitochondrial toxicity in CFS patients.

    In my opinion, the 'everyone is toxic' concept, is an 'easy sell' that lacks adequate scientific evidence. Most often, the toxin argument lacks any specific claims that can be independently verified by high quality clinical evidence. Which toxins? From where? What organelles can they be found in? What are the consequences to cell biochemistry?

    Even if we accept that we are exposed to more 'toxins' today compared to 60 years ago, what is the clear solid scientific evidence that shows the 'toxins bombarding and poisoning our our bodies' are causative of increased disease rates. Just to take one example. Benzene is a nasty chemical. Highly toxic. Exposure to benzene has been clearly shown to increase the likelihood of acute myeloid leukemia (AML). But the age-adjusted incidence rate for AML has changed very little over the last 60 years. Surely the toxin argument should mean that with benzene-derivatives being used so widely in our Westernized lifestyles, the age-adjusted incidence for AML should sky-rocket. But it hasnt. There are many other examples where a specific chemical has been shown to have a causative role in a specific cancer but the age-adjusted incidence rate has changed very little over the last 60 years.

    Now of course, we should avoid as many toxins in our environment/diet as possible, particularly with CFS. But apart from some obvious exceptions (asbestos and mesothelioma, or cigarettes and lung cancer just to name a couple), the actual epidemiological data suggests that, in general, we are not succumbing to an overload of toxins which results in (or contributes to) CFS.

    Also, to state the obvious, some individuals have diagnosed chemical sensitivities that can cause a whole range of serious heath issues. Clearly, such individuals need to be vigilant in avoiding chemicals and toxins. But it is not really valid to try and extrapolate observations from disease groups with diagnosed chemical sensitivities to a widespread chemical toxicity being responsible for significant numbers of CFS patients.

    What is perplexing to me is that simply declaring 'toxins' to be the culprit is often seen as a 'QED moment'. 'Toxins' seem to be a self-validating argument where critical analysis and evaluation of the data is not necessary. "Of course its the toxins, right?" A 'practitioner' will tell a patient that they have a 'build up of toxins' and they need to embark on a whole range of 'detox treatments' in order to cure themselves. The uncomfortable truth that toxins may not be responsible is often countered by 'practitioners' ordering in-house non-accredited tests for 'toxins' and heavy metals such as mercury, arsenic, cadmium, and lead (which very often come back positive). And a positive toxin report is all that is required to re-assure the patient that they need to embark on a detox program. Some detox programs advertised on the internet dont even make sense medically with claims that include 'inadvertently mobilizing toxins', 'detoxify in order to adapt and rebuild', 'timing detox to coincide with liver diurnal cycles', 'entering super detox mode' and so on. Rarely are such advertising descriptions backed by any sensible scientific description or publications.

    Again, there are some important exceptions. For example, NAC is used clinically to detox overdose patients. The ability of NAC to increase Glutathione in the liver and reduce free radical damage may have important therapeutic benefits in at least some CFS patients.

    But, I do agree: There is something intuitively appealing about the 'detox model'. For many the idea that we could take some natural herbs to gently help the liver to detox and free our bodies of toxic burdens..... well........ it just seems to make sense. But, in assessing different treatments, perhaps one consideration might be to recognize that while some 'pre-packaged concepts' might satisfy our intuitive beliefs, they may not make much scientific sense.

    Anyway, I guess no matter what our theories, we all know that the nature of the 'CFS beast' involves many treatment failures and very few treatment successes.

    Food for thought

    Rodger
     
  2. alex3619

    alex3619 Senior Member

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    Heavy metal toxicity, specifically, can be a major issue for mitochondria and energy metabolism.
     
    pattismith, ljimbo423 and Learner1 like this.
  3. Hip

    Hip Senior Member

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    That's a very good point. Whatever the factor causing the energy metabolism blockage , it must "unstick" itself pretty easily from whatever part of the energy metabolism mechanism it is blocking.

    I wonder if this fact might then rule out the idea of an ANT autoantibody blocking the translocator protein (ANT protein)? I don't have the knowledge to answer this question, but I imagine that an ANT autoantibody might bind reasonably tightly to its ANT protein target inside the cell, and would not be so easily dislodged by a change of the serum outside the cell, when the ME/CFS patients's serum is removed and replaced by a healthy person's serum.
     
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  4. alex3619

    alex3619 Senior Member

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    One of the big issues with thinking about toxins is about combinatorial impact. Traditionally, for toxin A, X amount of toxin is safe, and X+Y amount is unsafe. Yet what about impact from toxin A+B+C? There is little research on this. Furthermore our food and water is almost universally contaminated with huge numbers of substances that do not occur in nature in any quantity. We keep adding more and more to the environment, much faster than it degrades. We literally have no idea what it is all doing. When we do investigate we also typically look at single toxins, not combinations.

    Now I think the argument that there is no proof that most of these substances do harm is both accurate and highly misleading. Sure, most probably do no harm. Most. Yet the ones that do are unidentified and might do catastrophic harm.

    Now when it comes to non-toxic issues, how much do we know about the combination of bacterial or viral infections and a range of toxins? I suspect we know close to nothing. Similar arguments apply to genetic and dietary and other problems.
     
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  5. alex3619

    alex3619 Senior Member

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    I doubt it. Its more likely to be a weak binding, and easily dislodged. The only way it would be a strong binding is if there were a specific autoimmune response targeting that protein, and specifically that part of the protein outside the mitochondrial wall. I suspect its more likely to be weak specificity as to target ... but we lack good data in any case. Almost anything is possible without better data.

    Yet if its inside the cell then action outside the cell should not dislodge it. What might is a substantive change in pH, either low or high.
     
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  6. Hip

    Hip Senior Member

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    In the case of the ANT autoantibody found in coxsackievirus B myocarditis, the autoantibody that targets the ANT protein is thought to arise due to the fact that antibodies to the coxsackievirus B capsid protein are cross-reactive to ANT protein.

    So I guess that the strength by which this capsid protein antibody binds to the ANT protein will depend on how similar the capsid protein antigen is to the ANT protein antigen.
     
  7. alex3619

    alex3619 Senior Member

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    ... and how similar to that particular 3D conformation of the exposed protein. So its likely to be weak. pH can greatly modify that binding. Cross reactivity has little to do with protein sequence, its about conformation and charge.
     
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  8. Learner1

    Learner1 Professional Patient

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    Yes, its very likely. You need several other cofactors, adequate water and fiber consumption, and good elimination capability or whatever you've mobilized can't get out of your body and produces symptoms before being redeposited in your fat, bones, brain, mitochondria, etc.
     
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  9. Learner1

    Learner1 Professional Patient

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    I can only speak for myself. 18 months ago, I was sleeping 16 hours a day, I got rid of arsenic and lead that were measurable in both blood and urine under a competent doctor's supervision, and got down to sleeping 10 hours a day with improved cognitive function. I also have immunecsnd infection problems, so I wasn't cured, Working on these has removed my brain fog and got me sleeping 8-9 hours a day.

    I suspect most people have more than one problem to solve which is why this disease is so vexing. "I tried X and it didn't work..."

    The exception seems to be people with mold exposure, who seem to get well after treating just that.
    I don't know what is typical, but I live in the US and my doctor ordered the test (looking for possible causes of my cancer), which showed a couple of concerning chemicals as DNA adducts.

    Avoiding toxins is best. Being nutritionally replete helps avoid kicking up toxins as your body has the ability to run its detox processes in a continual basis.

    Mitochondria recycle every 6-8 weeks or so, so toxins are released and picked up again by the new ones, so having your detox processes running well will help them be eliminated rather than being picked up.

    In my case, as I was very toxic, I used an alpha lipoic acid polymer, PolyMVA, which greatly reduced my toxicity, along with curcumin and a comprehensive methylation protocol. I also used NT Factor to repair mitochondrial membranes.

    This process was doctor supervised and measurable on my labs and led to dramatically positive changes in my function.
    Yes, as described above. You need to have adequate cofactors for not just the folate cycle, but also the methionine cycle, glutathione production, and the trsnssulfuration pathway.

    These include B1, B2, B3, B6, B12, magnesium, potassium, selenium, molybdenum, trimethylglycine, glutamine, cysteine, glycine, and methionine, and antioxidants.

    If you just supplement 5-MTHF, but don't have adequate amounts of the other nutrients, you will run into trouble.
     
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  10. andyguitar

    andyguitar Senior Member

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    Hydrogen peroxide poisoning caused by the degradation of elevated levels of Serotonin.
     

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